Chemoprevention has become an effective cancer control modality, however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. Therefore, agents capable for inhibition of promotion stage of tumorigenesis with the ability to intervene at several critical pathways in the tumorigenesis process have greater advantage over other single-target agents are highly desirable.
To reduce the occurrence of cancer, one promising approach is its prevention, specifically by chemical intervention through minor non-nutrient dietary constituents. Important to chemoprevention is the fact that carcinogenesis is a long term process of cellular growth, division and subsequent clonal expansion of initiated cells exemplified by steps known as initiation, promotion and progression (Gupta and Mukhtar, 2002). One advantage of chemoprevention is that agents can be targeted against each stage of tumorigenesis. Thus, inhibition or slowing of any stage of carcinogenesis can potentially prevent cancers from becoming clinically significant.
The intervention of cancer at the promotion stage, however, seems to be most appropriate and practical. The major reason for this is the fact that tumor promotion is a reversible event at least in early stages and requires repeated and prolonged exposure of a promoting agent (Bickers and Athar, 2000). For this reason, it is important to identify anti-tumor promoting agents. A number of compounds have been evaluated by the inventors' laboratory and others, for their potential chemopreventive activity, and many of them are of plant origin (Gupta and Mukhtar, 2001). Therefore, considerable attention has been focused on identifying edible and medicinal phytochemicals that possess the ability to interfere with carcinogenic or mutagenic processes (Conney et al., 1997; Surh, 2003).
Lupeol [Lup-20(29)-en-3β-ol] is a naturally occurring triterpene found in various fruits, vegetables and in many medicinal plants (FIG. 1). Of particular note is that a significant quantity of this compound is present in olive, mango, strawberry and fig plants (Sosa, 1963; Anjaneyulu et al., 1982; Saeed and Sabir, 2002). Lupeol is found as an active constituent of various medicinal plants used by native people in the treatment of various skin aliments in North America, Japan, China, Latin America and Caribbean islands (Fournet et al., 1992; Lin et al., 2001; Miura et al., 2001; Beveridge et al., 2002; Kakuda et al., 2002; Badria et al., 2003; Santos Pereira and De Aquino Neto, 2003). Lupeol also has been shown to possess various pharmacological properties (Ulubelen et al., 1997; Geetha and Varalakshmi, 1999; Nagaraj et al., 2000; Sunitha et al., 2001; Vidya et al., 2002; Saleem et al., 2003). Lupeol has been shown to possess strong anti-inflammatory, anti-arthritic, anti-mutagenic and anti-malarial activity in vitro and in vivo systems (Guevara et al., 1996; Geetha and Varalakshmi, 1999; Geetha and Varalakshmi, 2001; Ziegler et al., 2002). Lupeol has been shown to act as a potent inhibitor of protein kinases and serine proteases (Hasmeda et al., 1999; Rajic et al., 2000; Hodges et al., 2003) and inhibit the activity of DNA topoisomerase II, a target for anti-cancer chemotherapy (Moriarity et al., 1998; Wada et al., 2001). Lupeol has also been shown to improve the epidermal tissue reconstitution (Nikiema et al., 2001). Recent studies have shown that Lupeol induces differentiation and inhibits cell growth of melanoma cells (Hata et al., 2002; 2003).